Smoked cannabis for chronic neuropathic pain: a randomized controlled trial

Background

Chronic neuropathic pain affects 1%–2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood.

Methods

Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events.

Results

We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02–1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough.

Conclusion

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063)Chronic neuropathic pain has a prevalence of 1%–2%,¹ and treatment options are limited.² Pharmacotherapy includes anticonvulsants, antidepressants, opioids and local anesthetics,^3,4 but responses vary and side effects limit compliance.Cannabis sativa has been used to treat pain since the third millennium BC.⁵ An endogenous pain-processing system has been identified, mediated by endogenous cannabinoid ligands acting on specific cannabinoid receptors.⁶ These findings, coupled with anecdotal evidence of the analgesic effects of smoked cannabis,⁷ support a reconsideration of cannabinoid agents as analgesics.Oral cannabinoids such as tetrahydrocannabinol, cannabidiol and nabilone have, alone and in combination, shown efficacy in central^8,9 and peripheral¹⁰ neuropathic pain, rheumatoid arthritis¹¹ and fibromyalgia.¹²The analgesic effects of smoked cannabis remain controversial, although it is used by 10%–15% of patients with chronic noncancer pain¹³ and multiple sclerosis.¹⁴ Clinical trials are needed to evaluate these effects, given that the risks and benefits of inhaled cannabinoids may differ from oral agents. To date, three small clinical trials of the analgesic efficacy of smoked cannabis have been reported.^15–17 All studies were conducted in residential laboratories, and participants smoked multiple doses of the drug at each time point. No study adequately reported data related to adverse events.We conducted a clinical trial using a standardized single-dose delivery system to explore further the safety and efficacy of smoked cannabis in outpatients with chronic neuropathic pain.     

Effectiveness of massage therapy for subacute low-back pain: a randomized controlled trial

BACKGROUND: The effectiveness of massage therapy for low-back pain has not been documented. This randomized controlled trial compared comprehensive massage therapy (soft-tissue manipulation, remedial exercise and posture education), 2 components of massage therapy and placebo in the treatment of subacute (between 1 week and 8 months) low-back pain. METHODS: Subjects with subacute low-back pain were randomly assigned to 1 of 4 groups: comprehensive massage therapy (n = 25), soft-tissue manipulation only (n = 25), remedial exercise with posture education only (n = 22) or a placebo of sham laser therapy (n = 26). Each subject received 6 treatments within approximately 1 month. Outcome measures obtained at baseline, after treatment and at 1-month follow-up consisted of the Roland Disability Questionnaire (RDQ), the McGill Pain Questionnaire (PPI and PRI), the State Anxiety Index and the Modified Schober test (lumbar range of motion). RESULTS: Of the 107 subjects who passed screening, 98 (92%) completed post-treatment tests and 91 (85%) completed follow-up tests. Statistically significant differences were noted after treatment and at follow-up. The comprehensive massage therapy group had improved function (mean RDQ score 1.54 v. 2.86-6.5, p < 0.001), less intense pain (mean PPI score 0.42 v. 1.18-1.75, p < 0.001) and a decrease in the quality of pain (mean PRI score 2.29 v. 4.55-7.71, p = 0.006) compared with the other 3 groups. Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function. At 1-month follow-up 63% of subjects in the comprehensive massage therapy group reported no pain as compared with 27% of the soft-tissue manipulation group, 14% of the remedial exercise group and 0% of the sham laser therapy group. INTERPRETATION: Patients with subacute low-back pain were shown to benefit from massage therapy, as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists.     

Acute pain therapy in postanesthesia care unit directed by skin conductance: a randomized controlled trial

Background

After surgery, effective and well-directed acute pain therapy is a necessary and integral part of the overall treatment plan. Generally, the assessment of pain intensity depends on a patient’s self-evaluation using scoring systems such as numeric rating scales (NRS, 0 to 10). Recently, a “Pain Monitor” was commercially provided which is based on measurements of fluctuations of skin conductance (NFSC). In this randomized, controlled, single-blind trial, possible benefits of this certain device were studied.

Methods

Postoperative patients (n = 44) were randomly assigned to a test or a control group during their stay in the postanesthesia care unit (PACU). All patients were treated and monitored according to internal hospital standards. Whereas all patients systematically evaluated their pain each 15 min, test group patients were additionally addressed when NFSC exceeded a predefined level. In cases of NRS≥5 during a routine elevation or in between, pain relief was achieved by standard procedures irrespective of group allocation.

Results

During their stay in PACU, both test and control groups experienced a significant decrease in NRS as a consequence of pain therapy. No significant differences in mean NRS or in NFSC values were found between the test and control groups. No correlation was observed between NRS and NFSC.

Conclusion

Postoperative patients experience diverse stressors, such as anxiety, disorientation, shivering, sickness and pain. Although the application of continuous pain monitoring would be meaningful in this clinical setting, the tested device failed to distinguish pain from other stressors in postoperative adult patients.

Trial Registration

German Clinical Trials Register DRKS00000755.     

Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial

Background

Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients.

Methods

Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance.

Findings

On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections.

Interpretation

PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections.

Trial Registration

Controlled-Trials.com ISRCTN74386719     

Effective neuropathic pain relief through sciatic nerve administration of GAD65-expressing rAAV2

Recently, we demonstrated that the administration of GAD65-expressing rAAV2 to DRG attenuates peripheral neuropathy by inducing GABA release in the spinal cord. However, the direct injection to DRG is invasive and may therefore cause nerve injury and other side effects.To circumvent this surgical intervention, we explored the potential of a much simpler and less invasive route of sciatic nerve administration. Using a neuropathic pain model, we introduced rAAV2-GAD65 through sciatic nerve and examined its therapeutic potency in pain-related behavior tests. Both GFP and GAD65 expression indicated that effective transgene delivery to the DRG can be accomplished via sciatic nerve administration. Equally importantly, the GABA concentration in the spinal cord increased significantly after GAD65 introduction, and pain symptoms were dramatically reduced and persistently controlled. The implication is that the sciatic nerve is a highly promising route for delivering rAAV2 to the DRG, and thus represents a much less invasive, clinically viable gene therapy option.     

Morphine: controlled trial of different methods of administration for postoperative pain relief.

Forty-five patients who had undergone major operations were given a slow intravenous injection of morphine sulphate (1 mg/ml saline) until their pain was relieved and were then randomly divided into three equal groups to receive different regimens of morphine sulphate over the next 72 hours. Patients in group A received 3.5 times the pain-relieving dose (28-63 mg, mean 36 mg) by continuous intravenous infusion; those in group B received the pain-relieving dose (90-160 mg, mean 110 mg) intramuscularly, four-hourly for the first 24 hours, six-hourly for the next 24 hours, and then eight and 20 hours later; and those in group C received the pain-relieving dose (80-280 mg, mean 140 mg) intramuscularly as required. Pain was assessed on a linear analogue scale and vital capacity and peak expiratory flow rate measured 12-hourly. The mean pain score was significantly lower and respiratory function significantly better in group A than in groups B and C. Only one patient (in group A) required extra morphine. Thus morphine administered by continuous intravenous infusion is superior to other regimens, giving better pain relief at a lower dosage.     

Acupuncture for migraine prophylaxis: a randomized controlled trial

Background:

Acupuncture is commonly used to treat migraine. We assessed the efficacy of acupuncture at migraine-specific acupuncture points compared with other acupuncture points and sham acupuncture.

Methods:

We performed a multicentre, single-blind randomized controlled trial. In total, 480 patients with migraine were randomly assigned to one of four groups (Shaoyang-specific acupuncture, Shaoyang-nonspecific acupuncture, Yangming-specific acupuncture or sham acupuncture [control]). All groups received 20 treatments, which included electrical stimulation, over a period of four weeks. The primary outcome was the number of days with a migraine experienced during weeks 5–8 after randomization. Our secondary outcomes included the frequency of migraine attack, migraine intensity and migraine-specific quality of life.

Results:

Compared with patients in the control group, patients in the acupuncture groups reported fewer days with a migraine during weeks 5–8, however the differences between treatments were not significant (p > 0.05). There was a significant reduction in the number of days with a migraine during weeks 13–16 in all acupuncture groups compared with control (Shaoyang-specific acupuncture v. control: difference –1.06 [95% confidence interval (CI) –1.77 to –0.5], p = 0.003; Shaoyang-nonspecific acupuncture v. control: difference –1.22 [95% CI –1.92 to –0.52], p < 0.001; Yangming-specific acupuncture v. control: difference –0.91 [95% CI –1.61 to –0.21], p = 0.011). We found that there was a significant, but not clinically relevant, benefit for almost all secondary outcomes in the three acupuncture groups compared with the control group. We found no relevant differences between the three acupuncture groups.

Interpretation:

Acupuncture tested appeared to have a clinically minor effect on migraine prophylaxis compared with sham acupuncture.

Trial Registration:

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00599586","term_id":"NCT00599586"}}NCT00599586About 6%–8% of men and 16%–18% of women in the United States and England experience migraines, with or without an aura.^1,2 A prevalence of 1% has been reported in mainland China,³ compared with 4.7% in Hong Kong and 9.1% in Taiwan.^4,5 A recent Cochrane meta-analysis suggests that acupuncture as migraine prophylaxis is safe and effective and should be considered as a treatment option for willing patients.⁶Although the specific effects acupuncture are controversial, acupuncture, as it is currently practised, clearly differentiates between real acupuncture points and nonacupuncture points. The Chinese Government launched the National Basic Research Program to obtain more data about the specificity of acupuncture points.⁷Trials from Italy and Brazil^8,9 showed that acupuncture was more effective than sham acupuncture in preventing migraines, but other trials have reported no differences.^10–13 There is no evidence that one acupuncture strategy is more effective than another for treating migraines. According to acupuncture theory, a headache on the lateral side is usually defined as a Shaoyang headache. In Jinkuiyi,¹⁴ migraines are said to affect the yang meridians (including the Taiyang, Yangming and Shaoyang meridians). In Lingshu,¹⁵ the Shaoyang meridians are said to go through the lateral side of the body, therefore the Shaoyang meridians are thought to be superior for treating migraines. Some points on the Shaoyang meridians are regarded as being more specific for migraines than other points.¹⁶Our aim was to investigate whether acupuncture at specific acupuncture points was more efficacious in preventing migraine than sham acupuncture at nonacupuncture points. We also investigated whether the efficacy varied when acupuncture points along different meridians or points along the same meridian were used.     

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial

BACKGROUND:Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain.METHODS:We randomly allocated children aged 8–17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes.RESULTS:A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval −7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9).INTERPRETATION:Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT02582307","term_id":"NCT02582307"}}NCT02582307

Abdominal pain is reported by a third of school-aged children¹ and accounts for several visits daily in most emergency departments.^2–5 Although the use of analgesia to treat acute abdominal pain is well-supported,^6,7 there is little evidence to guide the management of nonspecific abdominal pain in the emergency department,⁸ which accounts for two-thirds of cases of abdominal pain presenting to the emergency department.^8,9 Acetaminophen is the most commonly used World Health Organization Step 1 analgesic.¹⁰ In children, it is effective for many painful conditions,^11,12 but data supporting its use for abdominal pain are lacking.^13,14 Despite strong advocacy by the American Academy of Pediatrics¹⁵ for adequate pain management, less than two-thirds of children with abdominal pain in the emergency department receive analgesia,^16,17 and roughly half experience ongoing pain after discharge. ¹⁸ Children with nonspecific abdominal pain are less likely than those with a specific cause to receive analgesia.⁵ Available analgesic options for children with nonspecific abdominal pain in the emergency department may result in greater adherence to the American Academy of Pediatrics recommendations.Hyoscine butylbromide is orally administered and available in most Canadian emergency departments. We surmised that it may be effective for colicky abdominal pain owing to its antispasmodic properties.¹⁹ Ten placebo-controlled studies involving 3699 adults with functional abdominal pain showed hyoscine butylbromide to be beneficial, without serious adverse effects.^20–29 In the only pediatric study, hyoscine butylbromide, 10 mg given orally, was found to be beneficial compared to a homeopathic preparation in 204 children, with no serious adverse effects.³⁰ We sought to determine whether hyoscine butylbromide was superior to acetaminophen in relieving pain among children presenting to the emergency department with nonspecific colicky abdominal pain.     

The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial

ABSTRACT: BACKGROUND: Neck pain is one of the chief complains of patients with cervical spondylosis (CS). Both in China and worldwide, acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a protocol designed for a multi-centre, randomised, controlled trial to evaluate the effects of optimised acupuncture treatment for CS neck pain. The study aims to evaluate the effects of the optimised acupuncture treatment in real practice compared with sham and shallow acupuncture therapy. Methods/design This trial uses a multicentre, three-group, randomised, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. The sample size is calculated based on the formula for a three-group parallel design with a 0.05 significance level and a power of 0.9. A total of 105 cases in a single centre, and a total of 315 cases per each arm are required across all 9 centres. Patients who meet inclusion criteria are randomly assigned to receive optimised acupuncture treatment, sham acupuncture or shallow acupuncture by a computerised central randomisation system. The interventions last for 4 weeks with 8 to 10 treatments. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. DISCUSSION: This trial is a multicentre randomised control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomisation in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture versus placebo or non-classic acupuncture therapy and evaluate whether classic Chinese medical acupuncture is effective on CS neck pain. This study will provide evidence for the effects of acupuncture on CS neck pain. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-TRC-00000184.     

Liposomal lidocaine to improve procedural success rates and reduce procedural pain among children: a randomized controlled trial

BackgroundHistorically, children have been undertreated for their pain, and they continue to undergo painful cutaneous procedures without analgesics. A new topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR Pharma, Windsor, Ont.), has become available. It has pharmacologic properties that are superior to other topical anesthetics, including an onset of action of only 30 minutes. We sought to determine the success rate of cannulation, analgesic effectiveness, procedure duration and rate of adverse skin reactions when liposomal lidocaine is used before intravenous cannulation of children.MethodsIn this double-blind randomized controlled trial, children aged 1 month to 17 years received liposomal lidocaine or placebo before cannulation. Success on first cannulation attempt was recorded, and, among children 5 years and older, pain was evaluated before and after the attempt by the child, parents and research assistant using a validated measure (Faces Pain Scale-Revised). For children younger than 5 years, pain was evaluated by the parents and research assistant only. The total duration of the procedure and adverse skin reactions were also recorded.ResultsBaseline characteristics did not differ (p > 0.05) between children who received liposomal lidocaine (n = 69) and those who received placebo (n = 73). Cannulation on the first attempt was achieved in 74% of children who received liposomal lidocaine compared with 55% of those who received placebo (p = 0.03). Among children 5 years of age and older (n = 67), lower mean pain scores during cannulation were reported by those receiving liposomal lidocaine (p = 0.01). Similarly, lower mean pain scores during cannulation were reported by the parents and research assistant for all children who received liposomal lidocaine than for all those who received placebo (p < 0.001). The mean total procedure duration was shorter with liposomal lidocaine (6.7 v. 8.5 minutes; p = 0.04). The incidence of transient dermal changes was 23% in both groups (p = 1.0).ConclusionsUse of liposomal lidocaine was associated with a higher intravenous cannulation success rate, less pain, shorter total procedure time and minor dermal changes among children undergoing cannulation. Its routine use for painful cutaneous procedures should be considered whenever feasible.Painful medical procedures are routinely performed on children for diagnostic and therapeutic reasons. The provision of analgesia for these procedures, however, remains uncommon.¹ Untreated pain has both short-term and long-term consequences. In the short term, there is pain during the actual procedure. This contributes to a lack of cooperation by the child, unsuccessful procedure attempts, repeated attempts, additional pain and a prolonged total procedure time. In the long term, repeated painful procedures can lead to conditioned anxiety responses and increased pain perception.^2,3 Inadequate analgesia during an initial procedure may diminish analgesic effectiveness at subsequent procedures.⁴ Moreover, there is a relation between painful procedures in childhood and blood-injection-injury phobia,⁵ a condition that affects up to 10% of adults and may cause people to avoid medical care.⁶ In light of the cumulative evidence of the negative consequences of untreated pain in childhood, interventions are needed to diminish pain among children undergoing medical procedures and to facilitate successful completion of procedures.Intravenous cannulation is a common, painful medical procedure. Although local anesthetics reduce the pain of cannulation,^7,8,9,10,11 most preparations are not feasible for routine use. The “gold standard” for skin anesthesia, lidocaine–prilocaine 5% cream, requires a 60-minute application time. In addition, it causes vasoconstriction,¹² which potentially obscures landmarks and makes cannulation more difficult.¹³ Another commercially available preparation, amethocaine 4% gel, requires a 30-minute application time. However, it frequently causes vasodilatation and may induce hypersensitivity with repeated use.¹⁴ An alternative option, subcutaneous injection of lidocaine, requires only a few minutes to administer, but it is associated with an extra and painful puncture and is therefore not routinely used.¹⁵Liposomal lidocaine 4% cream¹⁶ (Maxilene, RGR Pharma, Windsor, Ont.) was launched in Canada in 2003. The liposome-encapsulated formulation protects the anesthetic from being metabolized too quickly.¹⁷ Liposomal lidocaine has the advantages of “needle-free” administration, a short onset of action and minimal vasoactive properties that minimize any potential interference with cannulation success. It is not associated with methemoglobinemia, a systemic side effect of lidocaine–prilocaine.¹⁸Among children, liposomal lidocaine is as effective as lidocaine–prilocaine for decreasing pain from venipuncture¹⁹ and intravenous cannulation,^20,21 and as effective as buffered lidocaine injection for decreasing intravenous cannulation pain.¹⁵ Previous studies have not compared liposomal lidocaine with placebo. We conducted such a comparison to determine whether liposomal lidocaine improves cannulation success rates. We also sought to determine whether it reduces pain and procedure duration and is associated with a low frequency of dermal reactions.     

Acupuncture for chronic prostatitis/chronic pelvic pain syndrome: study protocol for a randomized controlled trial

Background

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition affecting men of all ages. Acupuncture may be an effective treatment option for CP/CPPS, but evidence is limited. We propose to evaluate the effectiveness of acupuncture in a rigorously conducted trial.

Methods

Ten hospitals will recruit 440 participants with CP/CPPS in China from October 2017 to December 2019. Participants will be randomly allocated to acupuncture or sham acupuncture with a 1:1 ratio using computerized simple random sampling. The whole study consists of 2-week baseline, 8-week treatment, and 24-week follow up. Twenty 30-mintute sessions of acupuncture or sham acupuncture treatment will be provided between week 1 and 8. The two co-primary outcomes are the proportion of responders at week 8 and week 32. Secondary outcomes include proportion of responders in the two groups at different time points; change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score; change in the NIH-CPSI subscales; change in the International Prostate Symptom Score; change in the Hospital Anxiety and Depression Scale; expectation assessments; proportions of participants in each response category of the Global Response Assessment; change in the International Index of Erectile Function 5; change in the five-level EuroQol five-dimensional questionnaire and a visual analogue scale; and changes in peak and average urinary flow rate.

Discussion

This study will provide robust evidence on whether acupuncture is effective for relieving symptoms of CP/CPPS.

Trials registration

ClinicalTrials.gov, NCT03213938. Registered on 5 July 2017.

     

Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial

Backgrounds

Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.

Methods

A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.

Results

Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.

Conclusions

The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.

Trial Registration

Clinical trial registered with http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00799968","term_id":"NCT00799968"}}NCT00799968 (Identifier: {"type":"clinical-trial","attrs":{"text":"NCT 00799968","term_id":"NCT00799968"}}NCT 00799968)     

Parent-only treatment for childhood obesity: a randomized controlled trial

Parent-only (PO) treatments for childhood obesity are feasible, more cost-effective and potentially easier to disseminate. The objective of this study was to determine whether a PO treatment is not inferior to a parent + child (PC) treatment for childhood obesity. Eighty parent-child dyads with an 8-12 year old overweight or obese child (>85th BMI-P) were recruited and randomized into PO or PC treatment for childhood obesity. Parents or parent-child dyads attended 5-month treatment groups. Child and parent body size, child caloric intake, and child physical activity were assessed at baseline, post-treatment, and 6-months follow-up. Noninferiority testing using mixed linear models was used to compare PO treatment with PC treatment. Results showed that the PO group was not inferior to the PC group in terms of child weight loss. Results also showed that the PO group was not inferior to the PC group in terms of parent weight loss and child physical activity, but not child caloric intake. This study suggests that a PO treatment could provide similar results to PC in child weight loss and other relevant outcomes, and potentially could be more cost-effective and easier to disseminate. Although further research is needed, this study suggests that PO groups are a viable method for providing childhood obesity treatment.     

The effect of vapocoolant spray on pain due to intravenous cannulation in children: a randomized controlled trial

Background

Established noninvasive pharmacologic means of alleviating pain and anxiety in children undergoing intravenous cannulation are time-consuming, and thus impractical for routine use in the emergency department. Vapocoolant sprays provide transient skin anesthesia within seconds of application. We compared the effect of a new vapocoolant spray to placebo on pain due to intravenous cannulation in children.

Methods

In this double-blind randomized controlled trial, which we conducted between June 1 and Sept. 12, 2006, 80 children aged 6–12 years received either vapocoolant spray or placebo before cannulation. Children rated their pain using a 100-mm colour visual analogue scale. Secondary outcomes included success rate on first attempt at cannulation and pain ratings by the children''s parents, nurses and child life specialists.

Results

We found a modest but significant reduction in pain with the use of vapocoolant spray (mean difference 19 mm, 95% confidence interval [CI] 6–32 mm; p < 0.01). Cannulation on first attempt was more often successful with the use of vapocoolant spray (85.0%) than with placebo (62.5%) (mean difference 22.5%, 95% CI 3.2%–39.9%; p = 0.03). The number needed to treat to prevent 1 cannulation failure was 5 (95% CI 3–32). Parents (p = 0.04), nurses (p = 0.01) and child life specialists (p < 0.01) considered the children''s pain to be reduced with the use of vapocoolant spray.

Interpretation

The vapocoolant spray in our study quickly and effectively reduced pain due to intravenous cannulation in children and improved the success rate of cannulation. It is an important option to reduce childhood procedural pain in emergency situations, especially when time precludes traditional interventions.(http://ClinicalTrials.gov trial register no. {"type":"clinical-trial","attrs":{"text":"NCT00130650","term_id":"NCT00130650"}}NCT00130650.)Children frequently undergo intravenous cannulation in the emergency department. This painful procedure causes considerable stress and anxiety for children and their parents.¹ Failure to alleviate pain results in an uncooperative child, unsuccessful procedures (increased reattempts), prolonged procedure time and dissatisfaction with care for all involved.² Although pain may be reduced by behavioural and pharmacologic interventions (e.g., age-appropriate patient preparation, parental presence, distraction techniques, subcutaneous local anesthetics, topical anesthetic and systemic anesthetics), most of these preparations are impractical in nonelective settings because they are too time-consuming.^3–12 Novel delivery approaches and new medication compositions may decrease this time.^13,14 Vapocoolant sprays are rapid-acting alternatives to topical anesthetics. They provide transient anesthesia via evaporation-induced skin cooling, which reduces pain. Results from studies of earlier vapocoolant sprays indicated that they reduced pain due to vaccine injection in children and adults,^15–18 but not pain due to intravenous cannulation in children.^19,20 We sought to determine whether a new product, Pain Ease (Gebauer Company, Cleveland, Ohio), would reduce pain with intravenous cannulation in children.     

Aerobic exercise and snoring in overweight children: a randomized controlled trial

Objective: To determine whether regular aerobic exercise improves symptoms of sleep‐disordered breathing in overweight children, as has been shown in adults. Research Methods and Procedures: Healthy but overweight (BMI ≥85th percentile) 7‐ to 11‐year‐old children were recruited from public schools for a randomized controlled trial of exercise effects on diabetes risk. One hundred children (53% black, 41% male) were randomly assigned to a control group (n = 27), a low‐dose exercise group (n = 36), or a high‐dose exercise group (n = 37). Exercise groups underwent a 13 ± 1.5 week after‐school program that provided 20 or 40 minutes per day of aerobic exercise (average heart rate = 164 beats per minute). Group changes were compared on BMI z‐score and four Pediatric Sleep Questionnaire scales: Snoring, Sleepiness, Behavior, and a summary scale, Sleep‐Related Breathing Disorders. Analyses were adjusted for age. Results: Both the high‐dose and low‐dose exercise groups improved more than the control group on the Snoring scale. The high‐dose exercise group improved more than the low‐dose exercise and control groups on the summary scale. No group differences were found for changes on Sleepiness, Behavior, or BMI z‐score. At baseline, 25% screened positive for sleep‐disordered breathing; half improved to a negative screen after intervention. Discussion: Regular vigorous exercise can improve snoring, a symptom of sleep‐disordered breathing, in overweight children. Aerobic exercise programs may be valuable for prevention and treatment of sleep‐disordered breathing in overweight children.     

Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial

Introduction  

To elucidate in polymyalgia rheumatica (PMR) the role of tumor necrosis factor (TNF) α and the therapeutic potential of blockade with soluble TNF-α receptor, we carried out the first randomized controlled trial with etanercept in PMR.     

Amantadine for dyskinesias in Parkinson's disease: a randomized controlled trial

Background

Dyskinesias are some of the major motor complications that impair quality of life for patients with Parkinson''s disease. The purpose of the present study was to investigate the efficacy of amantadine in Parkinson''s disease patients suffering from dyskinesias.

Methods

In this multi-center, double-blind, randomized, placebo-controlled, cross-over trial, 36 patients with Parkinson''s disease and dyskinesias were randomized, and 62 interventions, which included amantadine (300 mg /day) or placebo treatment for 27 days, were analyzed. At 15 days after washout, the treatments were crossed over. The primary outcome measure was the changes in the Rush Dyskinesia Rating Scale (RDRS) during each treatment period. The secondary outcome measures were changes in the Unified Parkinson''s Disease Rating Scale part IVa (UPDRS-IVa, dyskinesias), part IVb (motor fluctuations), and part III (motor function).

Results

RDRS improved in 64% and 16% of patients treated with amantadine or placebo, respectively, with significant differences between treatments. The adjusted odds-ratio for improvement by amantadine was 6.7 (95% confidence interval, 1.4 to 31.5). UPDRS-IVa was improved to a significantly greater degree in amantadine-treated patients [mean (SD) of 1.83 (1.56)] compared with placebo-treated patients [0.03 (1.51)]. However, there were no significant effects on UPDRS-IVb or III scores.

Conclusions

Results from the present study demonstrated that amantadine exhibited efficacious effects against dyskinesias in 60–70% of patients.

Trial Registration

UMIN Clinical Trial Registry UMIN000000780     

Effectiveness of focused structural massage and relaxation massage for chronic low back pain: protocol for a randomized controlled trial

Background

Hypertension affects 29% of the adult U.S. population and is a leading cause of heart disease, stroke, and kidney failure. Despite numerous effective treatments, only 53% of people with hypertension are at goal blood pressure. The chronic care model suggests that blood pressure control can be achieved by improving how patients and physicians address patient self-care.

Methods and design

This paper describes the protocol of a nested 2 × 2 randomized controlled trial to test the separate and combined effects on systolic blood pressure of a behavioral intervention for patients and a quality improvement-type intervention for physicians. Primary care practices were randomly assigned to the physician intervention or to the physician control condition. Physician randomization occurred at the clinic level. The physician intervention included training and performance monitoring. The training comprised 2 internet-based modules detailing both the JNC-7 hypertension guidelines and lifestyle modifications for hypertension. Performance data were collected for 18 months, and feedback was provided to physicians every 3 months. Patient participants in both intervention and control clinics were individually randomized to the patient intervention or to usual care. The patient intervention consisted of a 6-month behavioral intervention conducted by trained interventionists in 20 group sessions, followed by 12 monthly phone contacts by community health advisors. Follow-up measurements were performed at 6 and 18 months. The primary outcome was the mean change in systolic blood pressure at 6 months. Secondary outcomes were diastolic blood pressure and the proportion of patients with adequate blood pressure control at 6 and 18 months.

Discussion

Overall, 8 practices (4 per treatment group), 32 physicians (4 per practice; 16 per treatment group), and 574 patients (289 control and 285 intervention) were enrolled. Baseline characteristics of patients and providers and the challenges faced during study implementation are presented. The HIP interventions may improve blood pressure control and lower cardiovascular disease risk in a primary care practice setting by addressing key components of the chronic care model. The study design allows an assessment of the effectiveness and cost of physician and patient interventions separately, so that health care organizations can make informed decisions about implementation of 1 or both interventions in the context of local resources.

Trial registration

ClinicalTrials.gov identifier NCT00201136     

Chest pain with nondiagnostic electrocardiogram in the emergency department: a randomized controlled trial of two cardiac marker regimens

BACKGROUND: Early detection of acute myocardial infarction (AMI) may save lives. In the emergency setting, it is unclear whether the early use of certain cardiac markers (myoglobin and cardiac troponin I [cTnI]) assists in making appropriate decisions whether to admit or discharge patients with chest pain of possible ischemic cause who have nondiagnostic electrocardiograms (ECGs). We performed a study to determine whether the addition of new cardiac markers in the emergency department results in improved clinical decisions. METHODS: A single-blind randomized controlled trial was conducted between June 1997 and June 1998 in a tertiary care emergency department in Kingston, Ont. Of 296 patients aged 30 years or more who presented to the emergency department with chest pain and nondiagnostic ECGs, 146 were randomly assigned to the intervention group (determination of baseline creatine kinase [CK] level, CK MB fraction and cTnI level, and myoglobin level at baseline and at 2 hours) and 150 to the control group (determination of baseline CK level and CK MB fraction). Outcome measures included the rate of admission to the inpatient cardiology service and length of stay in the emergency department. RESULTS: Of the 296 patients, 34 (11.5%) received a diagnosis of AMI in the emergency department, and 92 (31.1%) had chest pain of noncardiac cause. Patients in the intervention group were less likely than those in the control group to be admitted to the cardiology service (67 [45.9%] v. 81 [54.0%]). The absolute difference in the proportion (8.1% [95% confidence interval -3.3 to 19.5]), although potentially important clinically, was not statistically significant. The length of stay in the emergency department was essentially the same in the 2 study groups. At 30 days, the proportions of patients with a diagnosis of recurrent angina (58.2% in the intervention group and 58.0% in the control group) and AMI (12.3% and 14.7%) were also similar. INTERPRETATION: The optimal cardiac marker panel to be used in the emergency department remains unknown. The addition of serial testing of myoglobin with cTnI confirmation to the standard panel did not substantially change the clinical management or outcomes of patients presenting with chest pain and nondiagnostic ECGs.